In addition, administering methylxanthines (which increase respiratory drive) was linked with a more than 50% reduced risk of extubation failure (RR 0.48, 95% CI 0.32-0.71), the authors wrote in JAMA Pediatrics.

This was a systematic review conducted on 50 studies, all randomized clinical trials that enrolled intubated preterm infants, who were born prior to 37 weeks gestation.

"To our knowledge, this is the first review compiling the evidence for multiple interventions aimed at improving rates of successful extubation in preterm infants," the authors wrote, adding that two-thirds of all infants born prior to 29 weeks gestation require intubation.

"The authors have scrutinized an array of respiratory support measures including physical interventions and pharmacologic agents," they wrote. "The concise summary of the best evidence lends itself handy as a quick reference guide for various commonly debated support strategies."

There were 15 studies examining CPAP, and nine studies examining CPAP and head-box oxygen, head-to-head. While there was a significant difference in extubation failure rates, there was no such difference between the two methods in reintubation rates within 7 days (RR 0.83, 95% CI 0.66-1.04). The authors noted this may have been because "rescue CPAP" was used successfully in many studies when head-box oxygen failed.

Ten studies examined NIPPV, which the authors explained can be synchronized with the infant's breathing (S-NIPPV), non-synchronized with infant breathing (NS-NIPPV), or via biphasic positive airway pressure, which is delivered via "variable-flow" devices, and cycles between higher or lower set pressures, independent of breathing (BiPaP).

Twostudies and one Cochrane review found that any form of NIPPV was superior to CPAP in reducing risk of extubation failure and significantly reducing rates of reintubation (RR 0.74, 95% CI 0.64-0.85, NNT: 10). However, the authors noted a high level of heterogeneity between the studies (I²=66%).

A subgroup analysis found differential treatment effects, with S-NIPPV proving superior to CPAP (RR 0.25, 95% CI 0.15-0.41). There was still significant difference in extubation failure when comparing the NS-NIPPV or biphasic positive airway pressure to CPAP, but it was more modest (RR 0.64, 95% CI 0.44-0.95).

"Translating the evidence for this heterogeneous group of treatments into clinical practice is difficult because there appear to be differences in efficacy between NIPPV and BiPaP modalities," the authors wrote. Indeed, no studies examined BiPaP alone.

Examining pharmacological therapies, six studies included in the Cochrane review found administering methylxanthines prophylactically was superior to placebo. One study examined doxapram, a respiratory stimulant, compared with "standard treatment" with methylxanthines, but there was no significant difference in extubation failure (RR 0.80, 95% CI 0.22-2.97).

Three studies found that corticosteroids -- often given to infants to reduce inflammation from endotracheal tubes -- was initially linked with a significant reduced rate of extubation, but the difference was no longer significant once a random-effects model was used, the authors noted. They also cautioned that longer courses of corticosteroids were linked with a higher risk of neurodevelopmental problems, but infants with a high risk of bronchopulmonary dysplasia had a lower risk of death or cerebral palsy associated with corticosteroid exposure.

Study limitations included large variations in how studies defined the duration of a successful extubation, as well as inconsistent definitions of the term "respiratory failure" between studies.

"A standard definition for defining extubation success and failure should be encouraged to enable synthesis of the evidence," the authors noted.

The editorialists pointed out that the review included evidence from studies of infants from a "wide range of gestational ages (mean gestational age, 27 weeks) and therefore at a very different stage of lung maturation, leaving the question of age appropriateness of supporting measures widely unanswered. In particular, for infants from the lowest gestational age groups, effective means to facilitate extubation still need to be established."

Ferguson disclosed no relevant relationships with industry. One co-author disclosed support from Fisher and Paykel.

Zivanovic and Roehr disclosed no relevant relationships with industry.

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